JP4043764B2 - Organopolycarbosiloxane having a sugar residue and method for producing the same - Google Patents
Organopolycarbosiloxane having a sugar residue and method for producing the same Download PDFInfo
- Publication number
- JP4043764B2 JP4043764B2 JP2001348118A JP2001348118A JP4043764B2 JP 4043764 B2 JP4043764 B2 JP 4043764B2 JP 2001348118 A JP2001348118 A JP 2001348118A JP 2001348118 A JP2001348118 A JP 2001348118A JP 4043764 B2 JP4043764 B2 JP 4043764B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- organopolycarbosiloxane
- integer
- carbon atoms
- general formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H23/00—Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B15/00—Preparation of other cellulose derivatives or modified cellulose, e.g. complexes
- C08B15/05—Derivatives containing elements other than carbon, hydrogen, oxygen, halogens or sulfur
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B3/00—Preparation of cellulose esters of organic acids
- C08B3/22—Post-esterification treatments, including purification
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B33/00—Preparation of derivatives of amylose
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/04—Polysiloxanes
- C08G77/38—Polysiloxanes modified by chemical after-treatment
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/04—Polysiloxanes
- C08G77/38—Polysiloxanes modified by chemical after-treatment
- C08G77/382—Polysiloxanes modified by chemical after-treatment containing atoms other than carbon, hydrogen, oxygen or silicon
- C08G77/392—Polysiloxanes modified by chemical after-treatment containing atoms other than carbon, hydrogen, oxygen or silicon containing sulfur
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/42—Block-or graft-polymers containing polysiloxane sequences
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/48—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule in which at least two but not all the silicon atoms are connected by linkages other than oxygen atoms
- C08G77/50—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule in which at least two but not all the silicon atoms are connected by linkages other than oxygen atoms by carbon linkages
Abstract
Description
【0001】
【発明の属する技術分野】
本発明は、糖残基を有する新規なオルガノポリカルボシロキサンとその製造方法に関し、詳しくはチオエーテル結合を介してケイ素原子と単糖もしくは多糖の特定部位が結合している糖残基を有するオルガノポリカルボシロキサンとその製造方法に関する。
【0002】
【従来の技術】
従来から、糖類が生体機能をつかさどる重要な役割を演じていることが知られていたが、最近では、その立体構造に起因する特異な物質間相互作用が明らかにされつつあり、それらの機能を有効に利用した創薬や機能材料の開発が注目されている。そのような目的で、糖類を合成高分子と結合させる方法とそれらの応用の試みが知られている。有機ケイ素ポリマーは、生物学的に不活性なので、薬剤、医療材料、化粧料等としては、好適な材料であり、これまでに多くの糖残基を有するオルガノポリシロキサンとその製造方法が提案されている。例えば、糖類がアミド結合を介してポリシロキサンに結合したもの(特開昭62−68820号公報参照)、糖類がグリコシド結合を介してポリシロキサンに結合したもの(特開平5−186596号公報参照)、糖類がウレタン結合を介してポリシロキサンに結合したもの(特開平8−134103号公報参照)、糖類がグリコシド結合またはチオグリコシド結合を介してポリシロキサンに結合したもの(特開平11−92490号公報参照)等が提案されている。しかしながら、オルガノポリカルボシロキサン類への糖類の結合については、報告されていなかった。オルガノポリカルボシロキサンでは、オルガノポリシロキサンでは合成が難しいデンドリマー構造、ダンベル型構造といった特殊な分子構造を有する化合物を作ることができるので、高度な機能を付与することができると期待される。
【0003】
【発明が解決しようとする課題】
本発明者は上記問題点を解決すべく鋭意検討した結果、本発明に到達した。
すなわち、本発明の目的は、デンドリマー構造やダンベル型構造などの分子構造を取り得る糖残基を有する新規なオルガノポリカルボシロキサンとその製造方法に関し、詳しくは、チオエーテル結合を介してケイ素原子と単糖もしくは多糖の特定部位が結合している糖残基を有するオルガノポリカルボシロキサンとその製造方法を提供することにある。
【0004】
【問題を解決するための手段】
本発明は、一般式:{X1R1 aSiO(3-a)/2}x{R1 bSiO(4-b)/2}y[式中、R1は炭素原子数1〜10のアルキル基もしくはアリール基であり、X1はi=1とした場合の一般式:
【化3】
{式中、R1は前記に同じ、R2は炭素原子数2〜10のアルキレン基であり、R3は炭素原子数1〜10のアルキル基であり、iは1〜10の整数であり、biは0〜3の整数であり、ciは0〜3の整数であり、biとciの和は3以下であり、X1で示されるシリルアルキル基の繰り返し数または階層数がiのとき、Xi+1は一般式:−R4−S−R5−Y(式中、R4 、R5はそれぞれ独立に炭素原子数1〜20の2価の炭化水素基であり、YはR5との結合部位が酸素原子である置換もしくは非置換の単糖残基または多糖残基である。)で示される基である。}で示されるシリルアルキル基であり、aは0〜2の整数であり、bは0〜3の整数であり、xは2以上の整数、yは0以上の整数であり、各シロキサン構造単位が複数ある場合は、それらは互いに同じでも異なっていても良い。]で示され、1分子中に少なくとも2個の置換または非置換の糖残基を有するオルガノポリカルボシロキサン、および、一般式:{Z1R1 aSiO(3-a)/2}x{R1 bSiO(4-b)/2}y [式中、R1 、R2 、a、b、x、yは前記に同じであり、Z1はi=1とした場合の一般式:
【化4】
{式中、R1、R2、R3、bi、ciは前記に同じであり、Z1で示されるシリルアルキル基の繰り返し数または階層数がiのとき、Zi+1は一般式:−R2Q(式中、R2は前記に同じであり、Qはハロゲン原子、炭素原子数1〜10のアルキルスルホネート基、炭素原子数6〜20のアリールスルホネート基から選ばれる基である。)で示される基である。}で示されるシリルアルキル基である。]で示され、1分子中に少なくとも2個のQで示される基を有するオルガノポリカルボシロキサンと、M−S−R5−Y(式中、R5 およびYは前記に同じであり、Mはアルカリ金属またはアルカリ土類金属原子である。)で示される糖残基を有する金属チオラート化合物を縮合反応させることを特徴とする糖残基を有するオルガノポリカルボシロキサンの製造方法に関する。
【0005】
【発明の実施の形態】
本発明の糖残基を有するオルガノポリカルボシロキサンは、一般式:{X1R1 aSiO(3-a)/2}x {R1 bSiO(4-b)/2}yで示される。式中、R1は炭素原子数1〜10のアルキル基もしくはアリール基であり、アルキル基としては、メチル基,エチル基,プロピル基,ブチル基,ペンチル基,イソプロピル基,イソブチル基,シクロペンチル基,シクロヘキシル基が例示され、アリール基としては、フェニル基,ナフチル基が例示される。これらの中でもメチル基が好ましい。X1はi=1とした場合の一般式:
【化5】
で示されるシリルアルキル基であり、オルガノシロキサン中のケイ素原子に結合している。上式中、R1は前記に同じであり、R2は炭素原子数2〜10のアルキレン基であり、エチレン基,プロピレン基,ブチレン基,ヘキシレン基などの直鎖状アルキレン基;メチルメチレン基,メチルエチレン基,1−メチルペンチレン基,1,4−ジメチルブチレン基などの分岐状アルキレン基が例示される。これらの中でも、エチレン基,メチルメチレン基,ヘキシレン基,1−メチルペンチレン基,1,4−ジメチルブチレン基が好ましい。R3は炭素原子数1〜10のアルキル基であり、メチル基,エチル基,プロピル基,ブチル基,ペンチル基,イソプロピル基が例示される。これらの中でもメチル基またはエチル基が好ましい。ここで、iは1〜10の整数であり、biは0〜3の整数であり、ciは0〜3の整数であり、biとciの和は3以下である。
【0006】
X1で示されるシリルアルキル基の繰り返し数または階層数がiのとき、Xi+1は一般式:−R4−S−R5−Yで示される基であって、本発明のオルガノポリカルボシロキサンは1分子中に少なくとも2個の該糖残基を有する必要がある。分子内での複数の糖残基同士の相互作用により、効果的な活性の向上や単独糖残基にはない特異な性質の発現を期待できるからである。
【0007】
なお、該シリルアルキル基の繰り返し数とは、直鎖状分子構造を有する該シリルアルキル基中の一般式:
【化6】
(R1、R2、R3、bi、ciは前記と同様である。)で示される繰り返し単位の数である。また、該シリルアルキル基の階層数とは、分岐状分子構造を有する該シリルアルキル基中の一般式:
【化7】
(R1、R2、R3、bi、ciは前記と同様である。)で示される分子構造単位で構成される階層の数である。
【0008】
ここで、一般式:−R4−S−R5−Yで示される基をR6とすると、該シリルアルキル基の繰り返し数または階層数が1である場合には、X1は一般式:
【化8】
で示され、該シリルアルキル基の繰り返し数または階層数が2である場合には、X1は一般式:
【化9】
で示され、該シリルアルキル基の繰り返し数または階層数が3である場合に、X1は一般式:
【化10】
で示される。
【0009】
上記R6中のR4 、R5はそれぞれ独立に炭素原子数1〜20の2価の炭化水素基であり、エチレン基,プロピレン基,ブチレン基,ヘキシレン基などの直鎖状アルキレン基;メチルメチレン基,メチルエチレン基,1−メチルペンチレン基,1,4−ジメチルブチレン基などの分岐状アルキレン基;1,4−フェニレン基,1,3−フェニレン基,4,4‘−ビフェニレン基などのアリーレン基;1,4−ビス(メチレン)フェニレン基,2,2−(パラフェニレン)プロピレン基などのアラルキレン基が例示される。上記R6中のYはR5との結合部位が酸素原子である置換もしくは非置換の単糖残基または多糖残基であり、糖構造を構成する単糖単位としては、グルコピラノース(グルコース)、マンノース、アロース、アルトロース、ガラクトース、イドース、タロース、グロース、リボース、アラビノース、キシロース、フルクトース、フコース、N−アセチルグルコサミン、N−アセチルガラクトサミン、シアル酸およびそれらのエステル化体などが例示される。具体的にはグルコピラノシル基(グルコシル基)、マンノシル基、アロシル基、アルトロシル基、ガラクトシル基、イドシル基、タロシル基、グリシル基、リボシル基、アラビノシル基、キシロシル基、フコシル基、フルクトシル基、N−アセチルグルコサミニル基、N−アセチルガラクトサミニル基、シアリル基などの単糖残基とそれらのエステル化体;マントシル基、セロビオシル基、ラクトシル基、マンノトリオシル基、グロボトリアオシル基などのオリゴ糖残基およびそれらのエステル化体;セルロシル基、アミロシル基などの多糖類残基およびそのエステル化体が例示される。これらの中でも、糖単位の数が5個以下の単糖残基またはオリゴ糖残基であることが好ましい。なお、R5と結合するY中の酸素原子はグリコシド酸素原子であることが好ましい。
【0010】
このようなR6としては、以下の構造が具体的に例示される。なお下記化学式中のAcはアセチル基を意味する。
【化11】
【化12】
【化13】
【化14】
【化15】
【化16】
【化17】
【化18】
【0011】
本発明の糖残基を有するオルガノポリカルボシロキサンを表す一般式:{X1R1 aSiO(3-a)/2}x {R1 bSiO(4-b)/2}yにおいて、aは0〜2の整数、bは0〜3の整数、xは2以上の整数、yは0以上の整数であるが、各シロキサン構造単位が複数ある場合は、それらは互いに同じでも異なっていても良い。このような、オルガノポリカルボシロキサンとしては、具体的には次の一般式で示されるものが例示される。なお、式中、X1、R1は前記に同じであり、e、f、g、h、j、k、l、m、nは一分子中に存在するシロキサン単位の数を表す整数である。
【化19】
【化20】
(n≧1)
【化21】
(m≧2)
【化22】
(l≧1)
【化23】
(k≧1,j≧2)
【化24】
(h≧2,g≧1)
R1 fSi(OSiR1 2X1)4-f (f =0,1)
XeSi(OSiR1 2X1)4-e(e =0,1)
(X1SiO3/2)8
(SiO4/2)8(X1R1 2SiO1/2)8
【0012】
本発明の糖残基を有するオルガノカルボポリシロキサンは、一般式:{Z1R1 aSiO(3-a)/2}x{R1 bSiO(4-b)/2}y で示されるオルガノポリカルボシロキサンと、M−S−R5−Yで示される糖残基を有する金属チオラート化合物を縮合反応させることにより製造される。上式中、R1 、R2 、a、b、x、yは前記に同じであり、Z1はi=1とした場合の一般式:
【化25】
で示されるシリルアルキル基であり、オルガノシロキサン中のケイ素原子に結合している。上式中R1、R2、R3、bi、ciは前記に同じであり、前述した該シリルアルキル基の繰り返し数または階層数がiのとき、Zi+1は一般式:−R2Qで示される基であり、R2は前記に同じであり、Qはハロゲン原子、炭素原子数1〜10のアルキルスルホネート基、炭素原子数6〜20のアリールスルホネート基から選ばれる基である。Qのハロゲン原子としては、塩素原子、臭素原子、ヨウ素原子が例示され、アルキルスルホネート基としては、メタンスルホネート基、エタンスルホネート基;アリールスルホネート基としてはベンゼンスルホネート基、トルエンスルホネート基が例示される。
【0013】
M−S−R5−Yで示される糖残基を有する金属チオラート化合物中のR5 およびYは前記に同じである。Mはアルカリ金属またはアルカリ土類金属原子であり、リチウム、ナトリウム、カリウム、カルシウム、マグネシウムが例示される。なお、M−S−R5−Yで示される糖残基を有する金属チオラート化合物は一般に単離するのが困難なので、例えば、対応する糖残基を有するチオール化合物に金属または金属水素化物などを作用させる方法や、対応する糖残基を有するチオエステル化合物やチオエーテル化合物に金属を作用させる方法などにより、反応系中で生成させ、そのまま縮合反応に用いることが好ましい。
【0014】
本発明の糖残基を有するオルガノポリカルボシロキサンの製造原料である一般式:{Z1R1 aSiO(3-a)/2}x{R1 bSiO(4-b)/2}y で示されるオルガノポリカルボシロキサンは公知の方法で製造することができ、その製造方法は特に限定されない。例えば、特開平10−298288号公報や特開平11−343347号公報に示される方法で製造した分岐末端にケイ素原子結合水素原子を持つカルボシロキサンデンドリマーに、ハロゲン原子、アルキルスルホネート基あるいはアリールスルホネート基を有するアルケニル化合物をヒドロシリル化反応させることにより直接合成することもできるし、該カルボシロキサンデンドリマー分岐末端に導入した水酸基を利用することで、置換反応によってハロゲン原子を、エステル化反応によってアルキルスルホネート基あるいはアリールスルホネート基をそれぞれ導入することもできる。
【0015】
また、M−S−R5−Yで示される糖残基を有する金属チオラート化合物は、例えば、公知の方法で糖分子のグリコシド水酸基をアルケニルエーテルに変換し、そのアルケニル基にチオカルボン酸またはチオール化合物をラジカル開始剤の存在下に付加反応させ、それぞれ、チオエステル誘導体またはチオエーテル化合物に変換した後、それぞれ、アルカリ金属もしくはアルカリ土類金属の塩基またはアルカリ金属もしくはアルカリ土類金属を作用させることにより製造することができる。
【0016】
以上のような本発明の糖残基を有するオルガノポリカルボシロキサンは、チオエーテル結合を介してケイ素原子と単糖もしくは多糖の特定部位とが結合している糖残基を有しており、直鎖状分子構造から多数の分岐構造を有するデンドリマー構造までの様々な分子構造を持つことができるという特徴がある。そのため、薬理活性や生体適合性といった糖類が本来有する特性に加えて、分子内での糖残基同士の相互作用により効果的な活性向上や単独糖残基にはない特異な性質を発現することが可能であるので、化粧品用原料、光学異性体分離用素材、毒素やウイルス等の分離用医療用素材、医療用薬剤、農業用薬剤など様々な応用分野で有用であるという利点を有する。また、本発明の糖残基を有するオルガノポリカルボシロキサンを製造する方法は、該オルガノポリカルボシロキサンを効率よく製造できるという特徴がある。
【0017】
【実施例】
以下、本発明を実施例により説明する。実施例中、本発明の糖残基を有するオルガノポリカルボシロキサンの同定は、核磁気共鳴分析により行った。なお、以下に示す反応式、化学式および文中、Pt cat.は白金と1,1,3,3−テトラメチル−1,3−ジビニルジシロキサンの錯体、Acはアセチル基、DMFはN,N−ジメチルホルムアミド、AIBNはアゾビスイソブチロニトリル、Phはフェニル基をそれぞれ意味する。
【0018】
【参考例1】
特開平10−298288号公報に記載された方法で調製したテトラキス{トリス(ジメチルシロキシ)シリルプロピルジメチルシロキシ}シランを原料として、下記の反応により、テトラキス{トリス(ブロモプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シランを調製した。すなわち、テトラキス{トリス(ジメチルシロキシ)シリルプロピルジメチルシロキシ}シランに、触媒として白金と1,1,3,3−テトラメチル−1,3−ジビニルジシロキサンの錯体の存在下、アリロキシトリメチルシランを反応させ、テトラキス{トリス(トリメチルシロキシプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シランを得、それに過剰のメタノールを作用させ、トリメチルシロキシ基を脱離させ、テトラキス{トリス(ヒドロキシプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シランとした。次に、得られたテトラキス{トリス(ヒドロキシプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シランにピリジン中、塩化メタンスルホニルを作用させ、テトラキス{トリス(メタンスルホニロキシプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シランとし、ついでDMF中で臭化ナトリウムを反応させ、テトラキス{トリス(ブロモプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シランを得た。
【化26】
【0019】
【参考例2】
特開平10−298288号公報に記載された方法で調製したメチルトリス{トリス(ジメチルシロキシ)シリルプロピルジメチルシロキシ}シランを原料として、下記の反応により、メチルトリス{トリス(ブロモプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シランを調製した。すなわち、メチルトリス{トリス(ジメチルシロキシ)シリルプロピルジメチルシロキシ}シランに、触媒として白金と1,1,3,3−テトラメチル−1,3−ジビニルジシロキサンの錯体の存在下、アリロキシトリメチルシランを反応させ、メチルトリス{トリス(トリメチルシロキシプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シランを得、それに過剰のメタノールを作用させ、トリメチルシロキシ基を脱離させ、メチルトリス{トリス(ヒドロキシプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シランとした。次に、得られたメチルトリス{トリス(ヒドロキシプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シランにピリジン中、塩化メタンスルホニルを作用させ、メチルトリス{トリス(メタンスルホニロキシプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シランとし、ついで、DMF中で臭化ナトリウムを反応させ、メチルトリス{トリス(ブロモプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シランを得た。
【化27】
【0020】
【参考例3】
β−D−グルコピラノースを原料として、下記の反応により4−アセチルチオブチル2,3,4,6−テトラ−O−アセチル−β−D−グルコピラノシドを調製した。すなわち、β−D−グルコピラノースに無水酢酸中で酢酸ナトリウムを作用させ、全ての水酸基をアセチル化してアセチル2,3,4,6−テトラ−O−アセチル−β−D−グルコピラノシドとし、ついで、触媒としての三フッ化ホウ素ジエチルエーテラート存在下に1−ブテン−4−オールを作用させ、ブテニル2,3,4,6−テトラ−O−アセチル−β−D−グルコピラノシドとした。次に、得られたブテニル2,3,4,6−テトラ−O−アセチル−β−D−グルコピラノシドをジオキサン中、チオ酢酸と混合し、ラジカル開始剤のAIBNを加えて反応させ、4−アセチルチオブチル2,3,4,6−テトラ−O−アセチル−β−D−グルコピラノシドを得た。
【化28】
【0021】
【参考例4】
β−D−グルコピラノースを原料として、下記の反応により4−ベンジルチオブチルβ−D−グルコピラノシドを調製した。すなわち、β−D−グルコピラノースに無水酢酸中で酢酸ナトリウムを作用させ、全ての水酸基をアセチル化してアセチル 2,3,4,6−テトラ−O−アセチル−β−D−グルコピラノシドとし、ついで、触媒として三フッ化ホウ素ジエチルエーテラートの存在下に、1−ブテン−4−オールを作用させ、ブテニル2,3,4,6−テトラ−O−アセチル−β−D−グルコピラノシドとした。次に、得られたブテニル2,3,4,6−テトラ−O−アセチル−β−D−グルコピラノシドをジオキサン中、ベンジルチオールと混合し、ラジカル開始剤のAIBNを加えて反応させ、4−ベンジルチオブチル2,3,4,6−テトラ−O−アセチル−β−D−グルコピラノシドを調製した後、メタノール中でナトリウムメトキシドを作用させて脱アセチル化し、4−ベンジルチオブチルβ−D−グルコピラノシドを得た。
【化29】
【0022】
【実施例1】
参考例1で調製したテトラキス{トリス(ブロモプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シラン81mg(275mmol)と参考例3で調製した4−アセチルチオブチル2,3,4,6−テトラ−O−アセチル−β−D−グルコピラノシド474mg(0.990mmol)を無水DMF0.5mlと無水メタノール0.5mlに溶解し、混合液を室温で2時間攪拌した。そこへ、ナトリウムメトキシド62mg(1.12mmol)を加え、35℃で24時間攪拌した。酢酸0.5mlを加え、室温で10分間攪拌した後、反応液を減圧濃縮した。無水酢酸5mlとピリジン5mlを加えて混合した後、氷水にあけ、それをクロロホルムで3回抽出した。有機層を合せ、1N塩酸、飽和重曹水、ついで飽和食塩水で洗浄し、無水硫酸マグネシウムで乾燥した。濃縮後、生成物をカラムクロマトグラフィーおよびゲルパーミエーションクロマトグラムにより精製し、下式で示される糖残基を有するオルガノポリカルボシロキサン95mgを得た。
【化30】
1H 核磁気共鳴スペクトルデータ(溶媒:重クロロホルム)
δ0.06(bs, 96H), 0.09(s, 54H), 0.48(t, J=9 Hz, 9H), 0.63(t, J=9 Hz, 32H), 1.33(m, 9H), 1.5-1.7(m, 72H), 2.00(s, 36H), 2.02(s, 36H), 2.04(s, 36H), 2.08(s, 36H), 2.50(t, J=6 Hz, 48H), 3.5 (m, 12H), 3.7(m, 12H), 4.1(m, 12H), 4.20(m, 12H), 4.27(m, 12H), 4.50(d, J=8 Hz, 12H), 4.97(t, J=10Hz, 12H), 5.07(t, J=10Hz, 12H), 5.17(t, J=10Hz, 12H)
【0023】
【実施例2】
参考例2で調製したメチルトリス{トリス(ブロモプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シラン70mg(0.0312mmol)と参考例3で調製した4−アセチルチオブチル2,3,4,6−テトラ−O−アセチル−β−D−グルコピラノシド404mg(0.843mmol)を無水DMF0.5mlと無水メタノール0.5mlに溶解し、混合液を室温で2時間攪拌した。そこへ、ナトリウムメトキシド51mg(0.928mmol)を加え、35℃で24時間攪拌した。酢酸0.4mlを加え、室温で10分間攪拌した後、反応液を減圧濃縮した。無水酢酸5mlとピリジン5mlを加えて混合した後、氷水にあけ、それをクロロホルムで3回抽出した。有機層を合せ、1N塩酸、飽和重曹水、ついで飽和食塩水で洗浄し、無水硫酸マグネシウムで乾燥した。濃縮後、生成物をカラムクロマトグラフィーおよびゲルパーミエーションクロマトグラムにより精製し、下式で示される糖残基を有するオルガノポリカルボシロキサン125mgを得た。
【化31】
1H 核磁気共鳴スペクトルデータ(溶媒:重クロロホルム)
δ0.06(s, 3H), 0.07(s, 18H), 0.09(s, 54H), 0.48(t, J=9 Hz, 6H), 0.63(t, J=9 Hz, 24H), 1.33(m, 6H), 1.5-1.7(m, 54H), 2.00(s, 27H), 2.02(s, 27H), 2.04(s, 27H), 2.08(s, 27H), 2.50(t, J=6 Hz, 36H), 3.5 (m, 9H), 3.7(m, 9H), 4.1(m, 9H), 4.20(m, 9H), 4.27(m, 9H), 4.50(d, J=8 Hz, 9H), 4.97(t, J=10Hz, 9H), 5.07(t, J=10Hz, 9H), 5.17(t, J=10Hz, 9H)
【0024】
【実施例3】
参考例4で調製した4−ベンジルチオブチルβ−D−グルコピラノシド353mg(0.985mmol)を−35℃に冷却し、アンモニアガスを吹き込み、30mlのアンモニアを液化させ、金属ナトリウム226mg(9.85mmol)を加え、−35℃で30分間攪拌した。そこへ、塩化アンモニウム474mg(8.86mmol)、ジメトキシエタン3mlに溶解した参考例2で調製したメチルトリス{トリス(ブロモプロピルジメチルシロキシ)シリルプロピルジメチルシロキシ}シラン92mg(0.041mmol)を加え、攪拌し、アンモニアガスを気化させながら、室温まで徐々に戻した。濃縮後、生成物をカラムクロマトグラフィーおよびゲルパーミエーションクロマトグラムにより精製し、下式で示される糖残基を有するオルガノポリカルボシロキサン16mgを得た。
【化32】
1H 核磁気共鳴スペクトルデータ(溶媒:重水)
δ0.0(bs, 75H), 0.5 (t, J=9 Hz, 6H), 0.6 (m, 24H), 1.3-1.8(m, 60H), 2.5(m, 36H), 3.1(m, 9H), 3.2-3.4(m, 27H), 3.5-3.6(m, 18H), 3.8(m, 18H), 4.3(bd, 9H)[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a novel organopolycarbosiloxane having a sugar residue and a method for producing the same, and more specifically, an organopolysiloxane having a sugar residue in which a silicon atom and a specific part of a monosaccharide or polysaccharide are bonded via a thioether bond. The present invention relates to carbosiloxane and a method for producing the same.
[0002]
[Prior art]
Traditionally, it has been known that saccharides play an important role in controlling biological functions, but recently, specific interactions between substances due to their three-dimensional structures are being clarified. The development of effective drug discovery and functional materials is attracting attention. For such purposes, methods for combining saccharides with synthetic polymers and attempts to apply them are known. Since organosilicon polymers are biologically inert, they are suitable materials for drugs, medical materials, cosmetics, etc., and organopolysiloxanes having many sugar residues and methods for producing the same have been proposed so far. ing. For example, saccharides bonded to polysiloxane via an amide bond (see JP-A-62-268820), saccharides bonded to polysiloxane via a glycosidic bond (see JP-A-5-186596) Saccharides bonded to polysiloxane via urethane bonds (see JP-A-8-134103), saccharides bonded to polysiloxane via glycosidic bonds or thioglycoside bonds (JP-A-11-92490) Etc.) have been proposed. However, there has been no report on the binding of saccharides to organopolycarbosiloxanes. With organopolycarbosiloxane, it is possible to produce a compound having a special molecular structure such as a dendrimer structure or a dumbbell structure, which is difficult to synthesize with organopolysiloxane, and it is expected that a high level of functionality can be imparted.
[0003]
[Problems to be solved by the invention]
As a result of intensive studies to solve the above problems, the present inventor has reached the present invention.
That is, an object of the present invention relates to a novel organopolycarbosiloxane having a sugar residue capable of taking a molecular structure such as a dendrimer structure or a dumbbell structure, and a method for producing the same, and more specifically, a silicon atom and a single atom via a thioether bond. An object of the present invention is to provide an organopolycarbosiloxane having a sugar residue to which a specific site of sugar or polysaccharide is bonded, and a method for producing the same.
[0004]
[Means for solving problems]
The present invention is a compound represented by the general formula: {X 1 R 1 a SiO (3-a) / 2 } x {R 1 b SiO (4-b) / 2 } y [wherein R 1 has 1 to 10 carbon atoms. of an alkyl or aryl group, the general formula in the case of X 1 was i = 1:
[Chemical 3]
{Wherein R 1 is the same as above, R 2 is an alkylene group having 2 to 10 carbon atoms, R 3 is an alkyl group having 1 to 10 carbon atoms, and i is an integer of 1 to 10 , B i is an integer of 0 to 3, c i is an integer of 0 to 3, the sum of b i and c i is 3 or less, and the number of repetitions or the number of layers of the silylalkyl group represented by X 1 Is i, X i + 1 is a general formula: —R 4 —S—R 5 —Y (wherein R 4 and R 5 are each independently a divalent hydrocarbon group having 1 to 20 carbon atoms). Y is a group represented by a substituted or unsubstituted monosaccharide residue or polysaccharide residue in which the binding site to R 5 is an oxygen atom. }, A is an integer of 0 to 2, b is an integer of 0 to 3, x is an integer of 2 or more, y is an integer of 0 or more, and each siloxane structural unit When there are a plurality of them, they may be the same as or different from each other. And an organopolycarbosiloxane having at least two substituted or unsubstituted sugar residues in one molecule, and the general formula: {Z 1 R 1 a SiO (3-a) / 2 } x { R 1 b SiO (4-b) / 2 } y [wherein R 1 , R 2 , a, b, x, y are the same as above, and Z 1 is a general formula where i = 1:
[Formula 4]
{Wherein, R 1, R 2, R 3, b i, is c i is as defined above, when the number of repetitions or number of levels of the silyl group represented by Z 1 is i, Z i + 1 is generally Formula: —R 2 Q (wherein R 2 is the same as defined above, Q is a group selected from a halogen atom, an alkyl sulfonate group having 1 to 10 carbon atoms, and an aryl sulfonate group having 6 to 20 carbon atoms) It is a group represented by } Is a silylalkyl group. And M—S—R 5 —Y (wherein R 5 and Y are the same as defined above, and M is an organic polycarbosiloxane having at least two groups represented by Q in one molecule. Is an alkali metal or alkaline earth metal atom), and relates to a method for producing an organopolycarbosiloxane having a sugar residue, characterized in that a metal thiolate compound having a sugar residue represented by
[0005]
DETAILED DESCRIPTION OF THE INVENTION
The organopolycarbosiloxane having a sugar residue of the present invention is represented by the general formula: {X 1 R 1 a SiO (3-a) / 2 } x {R 1 b SiO (4-b) / 2 } y . In the formula, R 1 is an alkyl group having 1 to 10 carbon atoms or an aryl group, and examples of the alkyl group include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, an isopropyl group, an isobutyl group, a cyclopentyl group, A cyclohexyl group is exemplified, and examples of the aryl group include a phenyl group and a naphthyl group. Among these, a methyl group is preferable. X 1 is a general formula when i = 1:
[Chemical formula 5]
And is bonded to a silicon atom in the organosiloxane. In the above formula, R 1 is the same as above, R 2 is an alkylene group having 2 to 10 carbon atoms, a linear alkylene group such as an ethylene group, a propylene group, a butylene group, a hexylene group; a methylmethylene group And branched alkylene groups such as methylethylene group, 1-methylpentylene group and 1,4-dimethylbutylene group. Among these, an ethylene group, a methylmethylene group, a hexylene group, a 1-methylpentylene group, and a 1,4-dimethylbutylene group are preferable. R 3 is an alkyl group having 1 to 10 carbon atoms, and examples thereof include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, and an isopropyl group. Among these, a methyl group or an ethyl group is preferable. Here, i is an integer of 1 to 10, b i is an integer of 0 to 3, c i is an integer of 0 to 3, and the sum of b i and c i is 3 or less.
[0006]
When the number of repetitions or number of layers silylalkyl group represented by X 1 is i, X i + 1 is the general formula: a group represented by -R 4 -S-R 5 -Y, Oruganopori of the present invention Carbosiloxanes must have at least two such sugar residues in one molecule. This is because the interaction between a plurality of sugar residues in the molecule can be expected to improve the activity effectively and express unique properties not found in a single sugar residue.
[0007]
The repeating number of the silylalkyl group is a general formula in the silylalkyl group having a linear molecular structure:
[Chemical 6]
(R 1 , R 2 , R 3 , b i , and c i are the same as described above). The number of layers of the silylalkyl group is a general formula in the silylalkyl group having a branched molecular structure:
[Chemical 7]
(R 1 , R 2 , R 3 , b i , and c i are the same as described above).
[0008]
Here, when the group represented by the general formula: —R 4 —S—R 5 —Y is R 6 , when the number of repeating or the number of layers of the silylalkyl group is 1, X 1 represents the general formula:
[Chemical 8]
In the case where the number of repeating or the number of hierarchy of the silylalkyl group is 2, X 1 is represented by the general formula:
[Chemical 9]
X 1 is represented by the general formula: when the repeating number or the number of layers of the silylalkyl group is 3.
Embedded image
Indicated by
[0009]
R 4 and R 5 in R 6 are each independently a divalent hydrocarbon group having 1 to 20 carbon atoms, and a linear alkylene group such as an ethylene group, a propylene group, a butylene group, or a hexylene group; Branched alkylene group such as methylene group, methylethylene group, 1-methylpentylene group, 1,4-dimethylbutylene group; 1,4-phenylene group, 1,3-phenylene group, 4,4′-biphenylene group, etc. And an aralkylene group such as 1,4-bis (methylene) phenylene group and 2,2- (paraphenylene) propylene group. Y in R 6 is a substituted or unsubstituted monosaccharide residue or polysaccharide residue whose binding site to R 5 is an oxygen atom, and the monosaccharide unit constituting the sugar structure is glucopyranose (glucose). Mannose, allose, altrose, galactose, idose, talose, gulose, ribose, arabinose, xylose, fructose, fucose, N-acetylglucosamine, N-acetylgalactosamine, sialic acid and esterified products thereof. Specifically, glucopyranosyl group (glucosyl group), mannosyl group, allosyl group, altrosyl group, galactosyl group, idosyl group, tarosyl group, glycyl group, ribosyl group, arabinosyl group, xylosyl group, fucosyl group, fructosyl group, N-acetyl Monosaccharide residues such as glucosaminyl group, N-acetylgalactosaminyl group, sialyl group and their esterified products; such as mantosyl group, cellobiosyl group, lactosyl group, mannotriosyl group, globotriaosyl group, etc. Examples include oligosaccharide residues and esterified products thereof; polysaccharide residues such as cellulosyl groups and amylosyl groups and esterified products thereof. Among these, monosaccharide residues or oligosaccharide residues having 5 or less saccharide units are preferable. Note that the oxygen atom in Y bonded to R 5 is preferably a glycoside oxygen atom.
[0010]
As such R 6 , the following structures are specifically exemplified. In the chemical formula below, Ac means an acetyl group.
Embedded image
Embedded image
Embedded image
Embedded image
Embedded image
Embedded image
Embedded image
Embedded image
[0011]
In the general formula representing the organopolycarbosiloxane having a sugar residue of the present invention: {X 1 R 1 a SiO (3-a) / 2 } x {R 1 b SiO (4-b) / 2 } y , a Is an integer of 0 to 2, b is an integer of 0 to 3, x is an integer of 2 or more, and y is an integer of 0 or more. When there are a plurality of siloxane structural units, they are the same or different from each other. Also good. Specific examples of such organopolycarbosiloxanes include those represented by the following general formula. In the formula, X 1 and R 1 are the same as described above, and e, f, g, h, j, k, l, m, and n are integers representing the number of siloxane units present in one molecule. .
Embedded image
Embedded image
(N ≧ 1)
Embedded image
(M ≧ 2)
Embedded image
(L ≧ 1)
Embedded image
(K ≧ 1, j ≧ 2)
Embedded image
(H ≧ 2, g ≧ 1)
R 1 f Si (OSiR 1 2 X 1 ) 4-f (f = 0, 1)
X e Si (OSiR 1 2 X 1 ) 4-e (e = 0, 1)
(X 1 SiO 3/2 ) 8
(SiO 4/2 ) 8 (X 1 R 1 2 SiO 1/2 ) 8
[0012]
The organocarbopolysiloxane having a sugar residue of the present invention is represented by the general formula: {Z 1 R 1 a SiO (3-a) / 2 } x {R 1 b SiO (4-b) / 2 } y It is produced by subjecting an organopolycarbosiloxane and a metal thiolate compound having a sugar residue represented by M—S—R 5 —Y to a condensation reaction. In the above formula, R 1 , R 2 , a, b, x, and y are the same as above, and Z 1 is a general formula when i = 1:
Embedded image
And is bonded to a silicon atom in the organosiloxane. In the above formula R 1, R 2, R 3 , b i, c i is as defined above, when the number of repetitions or number of layers of said silylalkyl group described above is i, Z i + 1 is the general formula: - R 2 is a group represented by Q, R 2 is the same as defined above, and Q is a group selected from a halogen atom, an alkyl sulfonate group having 1 to 10 carbon atoms, and an aryl sulfonate group having 6 to 20 carbon atoms. is there. Examples of the halogen atom of Q include a chlorine atom, a bromine atom, and an iodine atom. Examples of the alkyl sulfonate group include a methane sulfonate group and an ethane sulfonate group; examples of the aryl sulfonate group include a benzene sulfonate group and a toluene sulfonate group.
[0013]
R 5 and Y in the metal thiolate compound having a sugar residue represented by M—S—R 5 —Y are the same as described above. M is an alkali metal or alkaline earth metal atom, and examples thereof include lithium, sodium, potassium, calcium, and magnesium. In addition, since a metal thiolate compound having a sugar residue represented by M-S-R 5 -Y is generally difficult to isolate, for example, a metal or metal hydride is added to a thiol compound having a corresponding sugar residue. It is preferable to produce it in a reaction system by a method of allowing it to act, a method of causing a metal to act on a thioester compound or thioether compound having a corresponding sugar residue, and using it in a condensation reaction as it is.
[0014]
General formula: {Z 1 R 1 a SiO (3-a) / 2 } x {R 1 b SiO (4-b) / 2 } y which is a raw material for producing an organopolycarbosiloxane having a sugar residue of the present invention The organopolycarbosiloxane represented by can be produced by a known method, and the production method is not particularly limited. For example, a halogen atom, an alkyl sulfonate group or an aryl sulfonate group is added to a carbosiloxane dendrimer having a silicon atom-bonded hydrogen atom at a branched end produced by the method described in JP-A-10-298288 or JP-A-11-343347. The alkenyl compound can be directly synthesized by hydrosilylation reaction, or by using a hydroxyl group introduced into the branched end of the carbosiloxane dendrimer, a halogen atom is substituted by a substitution reaction, an alkyl sulfonate group or an aryl by an esterification reaction. Each sulfonate group can also be introduced.
[0015]
In addition, the metal thiolate compound having a sugar residue represented by M—S—R 5 —Y is obtained by, for example, converting a glycoside hydroxyl group of a sugar molecule into an alkenyl ether by a known method, and converting the alkenyl group into a thiocarboxylic acid or a thiol compound. In the presence of a radical initiator, converted to a thioester derivative or thioether compound, respectively, and then reacted with an alkali metal or alkaline earth metal base or an alkali metal or alkaline earth metal, respectively. be able to.
[0016]
The organopolycarbosiloxane having a sugar residue of the present invention as described above has a sugar residue in which a silicon atom and a specific site of a monosaccharide or polysaccharide are bonded via a thioether bond, It has a feature that it can have various molecular structures from a molecular structure to a dendrimer structure having many branched structures. Therefore, in addition to the inherent properties of saccharides such as pharmacological activity and biocompatibility, effective activity is improved by the interaction between sugar residues in the molecule and unique properties not found in single sugar residues are expressed. Therefore, it has an advantage that it is useful in various application fields such as cosmetic raw materials, optical isomer separation materials, medical materials for separation such as toxins and viruses, medical drugs, and agricultural drugs. Moreover, the method for producing an organopolycarbosiloxane having a sugar residue according to the present invention is characterized in that the organopolycarbosiloxane can be produced efficiently.
[0017]
【Example】
Hereinafter, the present invention will be described with reference to examples. In the examples, the organopolycarbosiloxane having a sugar residue of the present invention was identified by nuclear magnetic resonance analysis. In the reaction formulas, chemical formulas and sentences shown below, Pt cat. Is a complex of platinum and 1,1,3,3-tetramethyl-1,3-divinyldisiloxane, Ac is an acetyl group, DMF is N, N- Dimethylformamide, AIBN means azobisisobutyronitrile, and Ph means a phenyl group.
[0018]
[Reference Example 1]
Using tetrakis {tris (dimethylsiloxy) silylpropyldimethylsiloxy} silane prepared by the method described in JP-A-10-298288 as a raw material, tetrakis {tris (bromopropyldimethylsiloxy) silylpropyldimethylsiloxy is obtained by the following reaction. } A silane was prepared. That is, allyloxytrimethylsilane is added to tetrakis {tris (dimethylsiloxy) silylpropyldimethylsiloxy} silane in the presence of a complex of platinum and 1,1,3,3-tetramethyl-1,3-divinyldisiloxane as a catalyst. Reaction is carried out to obtain tetrakis {tris (trimethylsiloxypropyldimethylsiloxy) silylpropyldimethylsiloxy} silane, which is treated with excess methanol to eliminate the trimethylsiloxy group, and tetrakis {tris (hydroxypropyldimethylsiloxy) silylpropyldimethyl. Siloxy} silane was used. Next, the resulting tetrakis {tris (hydroxypropyldimethylsiloxy) silylpropyldimethylsiloxy} silane is reacted with methanesulfonyl chloride in pyridine to produce tetrakis {tris (methanesulfonyloxypropyldimethylsiloxy) silylpropyldimethylsiloxy} silane. Then, sodium bromide was reacted in DMF to obtain tetrakis {tris (bromopropyldimethylsiloxy) silylpropyldimethylsiloxy} silane.
Embedded image
[0019]
[Reference Example 2]
Using methyltris {tris (dimethylsiloxy) silylpropyldimethylsiloxy} silane prepared by the method described in JP-A-10-298288 as a raw material, methyltris {tris (bromopropyldimethylsiloxy) silylpropyldimethylsiloxy is obtained by the following reaction. } A silane was prepared. Namely, methyltris {tris (dimethylsiloxy) silylpropyldimethylsiloxy} silane was treated with allyloxytrimethylsilane in the presence of a complex of platinum and 1,1,3,3-tetramethyl-1,3-divinyldisiloxane as a catalyst. Reaction is carried out to obtain methyltris {tris (trimethylsiloxypropyldimethylsiloxy) silylpropyldimethylsiloxy} silane, which is treated with excess methanol to eliminate the trimethylsiloxy group, methyltris {tris (hydroxypropyldimethylsiloxy) silylpropyldimethyl Siloxy} silane was used. Next, the resulting methyltris {tris (hydroxypropyldimethylsiloxy) silylpropyldimethylsiloxy} silane is allowed to react with methanesulfonyl chloride in pyridine to obtain methyltris {tris (methanesulfonyloxypropyldimethylsiloxy) silylpropyldimethylsiloxy} silane. Then, sodium bromide was reacted in DMF to obtain methyltris {tris (bromopropyldimethylsiloxy) silylpropyldimethylsiloxy} silane.
Embedded image
[0020]
[Reference Example 3]
4-acetylthiobutyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside was prepared by the following reaction using β-D-glucopyranose as a raw material. That is, β-D-glucopyranose is allowed to act on sodium acetate in acetic anhydride, and all hydroxyl groups are acetylated to acetyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside, 1-buten-4-ol was allowed to act in the presence of boron trifluoride diethyl etherate as a catalyst to give butenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside. Next, the resulting butenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside was mixed with thioacetic acid in dioxane, and the radical initiator AIBN was added and reacted to give 4-acetyl. Thiobutyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside was obtained.
Embedded image
[0021]
[Reference Example 4]
4-Benzylthiobutyl β-D-glucopyranoside was prepared by the following reaction using β-D-glucopyranose as a raw material. That is, β-D-glucopyranose is allowed to act on sodium acetate in acetic anhydride, and all hydroxyl groups are acetylated to acetyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside, 1-buten-4-ol was allowed to act in the presence of boron trifluoride diethyl etherate as a catalyst to give butenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside. Next, the resulting butenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside was mixed with benzyl thiol in dioxane, reacted with the radical initiator AIBN, and 4-benzyl After preparing thiobutyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside, it was deacetylated by acting sodium methoxide in methanol to give 4-benzylthiobutyl β-D-glucopyranoside Got.
Embedded image
[0022]
[Example 1]
81 mg (275 mmol) of tetrakis {tris (bromopropyldimethylsiloxy) silylpropyldimethylsiloxy} silane prepared in Reference Example 1 and 4-acetylthiobutyl 2,3,4,6-tetra-O-acetyl prepared in Reference Example 3 474 mg (0.990 mmol) of -β-D-glucopyranoside was dissolved in 0.5 ml of anhydrous DMF and 0.5 ml of anhydrous methanol, and the mixture was stirred at room temperature for 2 hours. Thereto was added 62 mg (1.12 mmol) of sodium methoxide, and the mixture was stirred at 35 ° C. for 24 hours. After adding 0.5 ml of acetic acid and stirring at room temperature for 10 minutes, the reaction solution was concentrated under reduced pressure. Acetic anhydride (5 ml) and pyridine (5 ml) were added and mixed, then poured into ice water and extracted three times with chloroform. The organic layers were combined, washed with 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate, and then saturated brine, and dried over anhydrous magnesium sulfate. After concentration, the product was purified by column chromatography and gel permeation chromatogram to obtain 95 mg of organopolycarbosiloxane having a sugar residue represented by the following formula.
Embedded image
1 H nuclear magnetic resonance spectrum data (solvent: deuterated chloroform)
δ0.06 (bs, 96H), 0.09 (s, 54H), 0.48 (t, J = 9 Hz, 9H), 0.63 (t, J = 9 Hz, 32H), 1.33 (m, 9H), 1.5-1.7 (m, 72H), 2.00 (s, 36H), 2.02 (s, 36H), 2.04 (s, 36H), 2.08 (s, 36H), 2.50 (t, J = 6 Hz, 48H), 3.5 (m, 12H), 3.7 (m, 12H), 4.1 (m, 12H), 4.20 (m, 12H), 4.27 (m, 12H), 4.50 (d, J = 8 Hz, 12H), 4.97 (t, J = 10Hz , 12H), 5.07 (t, J = 10Hz, 12H), 5.17 (t, J = 10Hz, 12H)
[0023]
[Example 2]
70 mg (0.0312 mmol) of methyltris {tris (bromopropyldimethylsiloxy) silylpropyldimethylsiloxy} silane prepared in Reference Example 2 and 4-acetylthiobutyl 2,3,4,6-tetra-O prepared in Reference Example 3 -404 mg (0.843 mmol) of acetyl-β-D-glucopyranoside was dissolved in 0.5 ml of anhydrous DMF and 0.5 ml of anhydrous methanol, and the mixture was stirred at room temperature for 2 hours. Thereto was added 51 mg (0.928 mmol) of sodium methoxide, and the mixture was stirred at 35 ° C. for 24 hours. After adding 0.4 ml of acetic acid and stirring at room temperature for 10 minutes, the reaction solution was concentrated under reduced pressure. Acetic anhydride (5 ml) and pyridine (5 ml) were added and mixed, then poured into ice water and extracted three times with chloroform. The organic layers were combined, washed with 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate, and then saturated brine, and dried over anhydrous magnesium sulfate. After concentration, the product was purified by column chromatography and gel permeation chromatogram to obtain 125 mg of organopolycarbosiloxane having a sugar residue represented by the following formula.
Embedded image
1 H nuclear magnetic resonance spectrum data (solvent: deuterated chloroform)
δ0.06 (s, 3H), 0.07 (s, 18H), 0.09 (s, 54H), 0.48 (t, J = 9 Hz, 6H), 0.63 (t, J = 9 Hz, 24H), 1.33 (m , 6H), 1.5-1.7 (m, 54H), 2.00 (s, 27H), 2.02 (s, 27H), 2.04 (s, 27H), 2.08 (s, 27H), 2.50 (t, J = 6 Hz, 36H), 3.5 (m, 9H), 3.7 (m, 9H), 4.1 (m, 9H), 4.20 (m, 9H), 4.27 (m, 9H), 4.50 (d, J = 8 Hz, 9H), 4.97 (t, J = 10Hz, 9H), 5.07 (t, J = 10Hz, 9H), 5.17 (t, J = 10Hz, 9H)
[0024]
[Example 3]
354 mg (0.985 mmol) of 4-benzylthiobutyl β-D-glucopyranoside prepared in Reference Example 4 was cooled to −35 ° C., and ammonia gas was blown to liquefy 30 ml of ammonia to obtain 226 mg (9.85 mmol) of metallic sodium. And stirred at −35 ° C. for 30 minutes. Thereto, 474 mg (8.86 mmol) of ammonium chloride and 92 mg (0.041 mmol) of methyltris {tris (bromopropyldimethylsiloxy) silylpropyldimethylsiloxy} silane prepared in Reference Example 2 dissolved in 3 ml of dimethoxyethane were added and stirred. While the ammonia gas was vaporized, the temperature was gradually returned to room temperature. After concentration, the product was purified by column chromatography and gel permeation chromatogram to obtain 16 mg of organopolycarbosiloxane having a sugar residue represented by the following formula.
Embedded image
1 H nuclear magnetic resonance spectrum data (solvent: heavy water)
δ0.0 (bs, 75H), 0.5 (t, J = 9 Hz, 6H), 0.6 (m, 24H), 1.3-1.8 (m, 60H), 2.5 (m, 36H), 3.1 (m, 9H) , 3.2-3.4 (m, 27H), 3.5-3.6 (m, 18H), 3.8 (m, 18H), 4.3 (bd, 9H)
Claims (4)
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2001348118A JP4043764B2 (en) | 2001-11-13 | 2001-11-13 | Organopolycarbosiloxane having a sugar residue and method for producing the same |
AT02803109T ATE356845T1 (en) | 2001-11-13 | 2002-11-12 | FUNCTIONAL ORGANOPOLYCARBOSILOXANES CONTAINING SACCHARIDES AND METHOD FOR THE PRODUCTION THEREOF |
EP02803109A EP1453888B1 (en) | 2001-11-13 | 2002-11-12 | Saccharide residue-functional organopolycarbosiloxanes and method for the preparation thereof |
PCT/JP2002/011806 WO2003042284A1 (en) | 2001-11-13 | 2002-11-12 | Saccharide residue-functional organopolycarbosiloxanes and method for the preparation thereof |
US10/494,232 US7649087B2 (en) | 2001-11-13 | 2002-11-12 | Saccharide residue-functional organopolycarbosiloxanes and method for the preparation thereof |
DE60218891T DE60218891T2 (en) | 2001-11-13 | 2002-11-12 | SACCHARIDE-CONTAINING FUNCTIONAL ORGANOPOLYCARBOSILOXANES AND PROCESS FOR THEIR PREPARATION |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2001348118A JP4043764B2 (en) | 2001-11-13 | 2001-11-13 | Organopolycarbosiloxane having a sugar residue and method for producing the same |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2003146991A JP2003146991A (en) | 2003-05-21 |
JP4043764B2 true JP4043764B2 (en) | 2008-02-06 |
Family
ID=19160993
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2001348118A Expired - Fee Related JP4043764B2 (en) | 2001-11-13 | 2001-11-13 | Organopolycarbosiloxane having a sugar residue and method for producing the same |
Country Status (6)
Country | Link |
---|---|
US (1) | US7649087B2 (en) |
EP (1) | EP1453888B1 (en) |
JP (1) | JP4043764B2 (en) |
AT (1) | ATE356845T1 (en) |
DE (1) | DE60218891T2 (en) |
WO (1) | WO2003042284A1 (en) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4751570B2 (en) * | 2002-09-11 | 2011-08-17 | 東レ・ダウコーニング株式会社 | Organopolysiloxane-modified polysaccharide and method for producing the same |
FR2867480B1 (en) * | 2004-03-10 | 2008-08-08 | Rhodia Chimie Sa | GRAFTED POLYMER COMPRISING A POLYORGANOSILOXANE SKELET AND GLYCOSIDE PATTERNS |
CN101080436B (en) * | 2004-12-16 | 2010-09-22 | 陶氏康宁公司 | Ester derivatives of ascorbic and 2-keto acid saccharides |
ATE526365T1 (en) | 2004-12-23 | 2011-10-15 | Dow Corning | CROSS-LINKABLE SACCHARIDE-SILOXANE COMPOSITIONS AND NETWORKS, COATINGS AND ARTICLES FORMED THEREFROM |
WO2006127882A2 (en) * | 2005-05-23 | 2006-11-30 | Dow Corning Corporation | Surface treatment compositions comprising saccharide-siloxane copolymers |
KR101261256B1 (en) * | 2005-05-23 | 2013-05-07 | 다우 코닝 코포레이션 | Personal care compositions comprising saccharide-siloxane copolymers |
JP5185259B2 (en) * | 2006-05-23 | 2013-04-17 | ダウ・コーニング・コーポレイション | Novel silicone film forming agent for active ingredient delivery |
CN101641396B (en) | 2007-03-30 | 2012-08-22 | 日油株式会社 | Sugar alcohol-modified organopolysiloxane compound and method for producing the same |
CN102906161B (en) | 2010-04-30 | 2014-10-22 | 道康宁东丽株式会社 | Novel organopolysiloxane, surfactant, emulsion composition, powder treatment agent, thickening agent of oil-based raw material, gelling agent, gel composition, and cosmetic raw material comprising novel organopolysiloxane, as well as, preparation for external use and cosmetic comprising the same |
EP2563844A1 (en) * | 2010-04-30 | 2013-03-06 | Dow Corning Toray Co., Ltd. | Organopolysiloxane and use thereof as surfactant, powder treatment agent, thickening agent of oil -based raw material or gelling agent. gel and emulsion compositions, as well as, preparations for external use and cosmetics comprising the same |
CN103079539A (en) * | 2010-07-30 | 2013-05-01 | 道康宁东丽株式会社 | Cosmetic for hair containing sugar alcohol-modified silicone |
CN103068887B (en) | 2010-08-23 | 2015-09-09 | 道康宁公司 | Sugared siloxanes stable in aqueous environments and the preparation and application of these sugared siloxanes |
JP5756344B2 (en) * | 2011-05-30 | 2015-07-29 | 東レ・ダウコーニング株式会社 | Novel liquid organopolysiloxane and use thereof |
JP5809849B2 (en) * | 2011-05-30 | 2015-11-11 | 東レ・ダウコーニング株式会社 | Method for producing low odor sugar alcohol-modified silicone |
WO2012165228A1 (en) | 2011-05-30 | 2012-12-06 | 東レ・ダウコーニング株式会社 | Novel organo polysiloxane elastomer and use therefor |
JP6063197B2 (en) | 2012-10-02 | 2017-01-18 | 東レ・ダウコーニング株式会社 | Novel co-modified organopolysiloxane, powder treating agent and powder composition containing the same |
DE102013102239A1 (en) * | 2013-03-06 | 2014-09-11 | Universität Zu Köln | Carbosilane-containing fire-extinguishing foam |
JPWO2015162904A1 (en) | 2014-04-21 | 2017-04-13 | 東レ・ダウコーニング株式会社 | Method for producing liquid high-purity sugar derivative-modified silicone or composition thereof |
JP7463377B2 (en) | 2018-12-31 | 2024-04-08 | ダウ シリコーンズ コーポレーション | Silicon glycan and method for its preparation |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3914214A (en) * | 1973-08-24 | 1975-10-21 | Us Agriculture | Thiolation of polysaccharides |
JPS6268820A (en) | 1985-09-19 | 1987-03-28 | Kao Corp | Production of organopolysiloxane having saccharide residue |
JPH01192490A (en) * | 1988-01-22 | 1989-08-02 | Mazda Motor Corp | Marking device onto car body |
JP3172787B2 (en) | 1992-01-14 | 2001-06-04 | 日本精化株式会社 | Organosiloxane derivative having sugar residue and method for producing the same |
DE4437886A1 (en) * | 1994-10-22 | 1996-07-04 | Max Planck Gesellschaft | New mono- or polyhydroxylated (carbo)silane cpds. |
JP3009090B2 (en) | 1994-11-08 | 2000-02-14 | 信越化学工業株式会社 | Siloxane-containing pullulan and method for producing the same |
DE4441391A1 (en) * | 1994-11-21 | 1996-05-23 | Max Planck Gesellschaft | Modified poly:silane for control of solubility in water and oil |
JP3797519B2 (en) | 1997-02-28 | 2006-07-19 | 東レ・ダウコーニング株式会社 | Branched siloxane / silalkylene copolymer |
JP3827396B2 (en) * | 1997-03-17 | 2006-09-27 | Hoya株式会社 | Silicone-modified derivative of glucopyranose, polymer obtained using the same, contact lens material, and contact lens |
JPH1192490A (en) | 1997-07-25 | 1999-04-06 | Sagami Chem Res Center | Organosiloxane compound having saccharide residue and percutaneous absorption accelerator |
JP4383555B2 (en) | 1998-05-29 | 2009-12-16 | 東レ・ダウコーニング株式会社 | Carbosiloxane dendrimer |
US6177553B1 (en) * | 1998-08-07 | 2001-01-23 | Synsorb Biotech, Inc. | Solid phase synthesis of thio-oligosaccharides |
JP4043765B2 (en) * | 2001-11-13 | 2008-02-06 | 東レ・ダウコーニング株式会社 | Organopolysiloxane having sugar residue and process for producing the same |
-
2001
- 2001-11-13 JP JP2001348118A patent/JP4043764B2/en not_active Expired - Fee Related
-
2002
- 2002-11-12 DE DE60218891T patent/DE60218891T2/en not_active Expired - Lifetime
- 2002-11-12 US US10/494,232 patent/US7649087B2/en not_active Expired - Fee Related
- 2002-11-12 EP EP02803109A patent/EP1453888B1/en not_active Expired - Lifetime
- 2002-11-12 AT AT02803109T patent/ATE356845T1/en not_active IP Right Cessation
- 2002-11-12 WO PCT/JP2002/011806 patent/WO2003042284A1/en active IP Right Grant
Also Published As
Publication number | Publication date |
---|---|
EP1453888A1 (en) | 2004-09-08 |
EP1453888B1 (en) | 2007-03-14 |
JP2003146991A (en) | 2003-05-21 |
ATE356845T1 (en) | 2007-04-15 |
US20050043365A1 (en) | 2005-02-24 |
DE60218891T2 (en) | 2007-12-06 |
DE60218891D1 (en) | 2007-04-26 |
WO2003042284A1 (en) | 2003-05-22 |
US7649087B2 (en) | 2010-01-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4043764B2 (en) | Organopolycarbosiloxane having a sugar residue and method for producing the same | |
US7354982B2 (en) | Saccaride residue-functional organopolysiloxanes and method for the preparation thereof | |
Schwarz et al. | A broadly applicable method for the efficient synthesis of α-O-linked glycopeptides and clustered sialic acid residues | |
JPH0138798B2 (en) | ||
BRPI0711835A2 (en) | hybrid polyol (s) based compounds and based on at least one other molecular entity, whether or not polymeric, in particular of the polyorganosiloxane type, their preparation process and their applications | |
Chatterjee et al. | Chemical synthesis and seroreactivity of O-(3, 6-di-O-methyl-β-d-glucopyranosyl)-(1→ 4)-O-(2, 3-di-O-methyl-α-lrhamnopyranosyl)-(1→ 9)-oxynonanoyl-bovine serum albumin—the leprosy-specific, natural disaccharide-octyl-neoglycoprotein | |
Abronina et al. | The use of silyl groups in the synthesis of arabinofuranosides | |
JP4036755B2 (en) | Method for producing hyaluronic acid or hyaluronic acid derivative | |
Haupt et al. | Carbohydrate modified polydimethylsiloxanes. Part 1. Synthesis and characterization of carbohydrate silane and siloxane building blocks | |
CA2118405A1 (en) | Immunosuppressive and tolerogenic modified lewisc and lacnac compounds | |
CN108530570A (en) | The preparation method of polynorbonene backbone glycopolymers and its application in the synthesis of fucoidan analogies | |
JPH0616692A (en) | New sugar derivative | |
Cornil et al. | Multigram synthesis of an orthogonally-protected pentasaccharide for use as a glycan precursor in a Shigella flexneri 3a conjugate vaccine: application to a ready-for-conjugation decasaccharide | |
Daum et al. | Synthesis of a Fluorinated Sialophorin Hexasaccharide–Threonine Conjugate for Fmoc Solid‐Phase Glycopeptide Synthesis | |
US5910579A (en) | Processes for the preparation of αGal(1->4)βGal (1->4) Glc-OR | |
JP4890805B2 (en) | O-linked sugar amino acid derivative having core 3 type structure and method for producing the same | |
CA1111418A (en) | Synthesis of 2-amino-2-deoxyglycoses and 2-amino-2- deoxyglycosides from glycals | |
Litjens et al. | Synthesis of an α‐Gal epitope α‐d‐Gal p‐(1→ 3)‐β‐d‐Galp‐(1→ 4)‐β‐d‐Glc p NAc–lipid conjugate | |
Caulfield | The synthesis of glycosphingolipids: I.~ The synthesis of lactosylceramide and lactosylsphingenine and a short synthesis of triacetyl-D-Erythro-sphingosine. II.~ The synthesis of the Le (x) family of glycosphingolipids | |
JPH0196A (en) | α-(2-azido-2-deoxyglycosyl)ceramide derivative | |
JP2732084B2 (en) | Sugar chain for glycosyltransferase substrate and method for producing the same | |
JPH04266897A (en) | Glycolipid and production thereof | |
KR940005675A (en) | Polymer Lewis X (x) saccharides and preparation method thereof | |
Gan | Design and syntheses of multivalent glycoconjugates containing sialic acid. | |
JPH0195A (en) | α-glycosylceramide derivative |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20041111 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070605 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20071030 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20071114 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 4043764 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101122 Year of fee payment: 3 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101122 Year of fee payment: 3 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111122 Year of fee payment: 4 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111122 Year of fee payment: 4 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121122 Year of fee payment: 5 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121122 Year of fee payment: 5 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131122 Year of fee payment: 6 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313111 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
LAPS | Cancellation because of no payment of annual fees |